Childhood abuse and parental neglect are increasingly linked to adverse outcomes in adulthood, yet the specific neurobiological events that transduce early trauma to a myriad of problems in later life remain largely unknown. Patterns of anatomical connectivity within the brain are the foundations of its functional organization. By close integration with the proposed fMRI studies of Project 0012 and the proposed Primate Core, this project would apply cutting edge MRI technology and approaches to a characterization of the impact of childhood abuse/early trauma, and its developmental course, on brain structure and connectivity. The proposed project would test an overarching hypothesis of childhood abuse as a precipitant of neurodevelopmental abnormalities. Specific hypotheses to be tested include: that childhood abuse/early trauma is associated with a disorganization of extrinsic connectivity of brain networks subserving the stress response and hippocampal function (Aim 1), and salience attribution, mood regulation and emotion processing (Aim 2); and that early trauma is associated with deficits in the developmental maturation of the brain at multiple levels reflected in the volume, white matter integrity and extrinsic connectivity of brain areas (Aim 3). For Aim 1, four groups of women reflecting the different association possibilities of histories of childhood abuse and major depression (ie., +/+, +/-, -/+, -/-) would be compared by the results of fractional anisotropy (FA) brain maps derived from diffusion tensor imaging (DTI) and by baseline functional connectivity (FC) brain maps derived from low frequency time course correlation analyses of resting state images. For Aim 2, group differences in anatomic and functional connectivity for neural circuits involved in a negative mood state, and emotion and incentive salience processing would be defined using the task-related activation volumes identified in Project 0012 to define ROI and seed clusters in FA and FC analyses, respectively. For Aim 3, longitudinal MRI imaging in monkeys subjected to an intermittent maternal separation paradigm would define the developmental impact of early trauma on brain structural volumes and their extrinsic connectivity (DTI). This knowledge would frame the neurobiological impact of early trauma, provide a reference for understanding its role in the diathesis of subsequent mood and anxiety disorders, and drug abuse and dependence, and aid the design of treatment plans seeking to limit the adverse consequences of childhood abuse.